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. 2024 Jan;45(1):e26532.
doi: 10.1002/hbm.26532. Epub 2023 Nov 27.

Cortical gray to white matter signal intensity ratio as a sign of neurodegeneration and cognition independent of β-amyloid in dementia

Xiaomeng Xu  1 , Ikbeom Jang  2   3   4 , Junfang Zhang  1 , Miao Zhang  5 , Lijun Wang  1 , Guanyu Ye  1 , Aonan Zhao  1 , Yichi Zhang  1 , Biao Li  5 , Jun Liu  1   6 , Binyin Li  1   6 ; Alzheimer's Disease Neuroimaging Initiative
Affiliations

Cortical gray to white matter signal intensity ratio as a sign of neurodegeneration and cognition independent of β-amyloid in dementia

Xiaomeng Xu et al. Hum Brain Mapp. 2024 Jan.

Abstract

Cortical gray to white matter signal intensity ratio (GWR) measured from T1-weighted magnetic resonance (MR) images was associated with neurodegeneration and dementia. We characterized topological patterns of GWR during AD pathogenesis and investigated its association with cognitive decline. The study included a cross-sectional dataset and a longitudinal dataset. The cross-sectional dataset included 60 cognitively healthy controls, 61 mild cognitive impairment (MCI), and 63 patients with dementia. The longitudinal dataset included 26 participants who progressed from cognitively normal to dementia and 26 controls that remained cognitively normal. GWR was compared across the cross-sectional groups, adjusted for amyloid PET. The correlation between GWR and cognition performance was also evaluated. The longitudinal dataset was used to investigate GWR alteration during the AD pathogenesis. Dementia with β-amyloid deposition group exhibited the largest area of increased GWR, followed by MCI with β-amyloid deposition, MCI without β-amyloid deposition, and controls. The spatial pattern of GWR-increased regions was not influenced by β-amyloid deposits. Correlation between regional GWR alteration and cognitive decline was only detected among individuals with β-amyloid deposition. GWR showed positive correlation with tau PET in the left supramarginal, lateral occipital gyrus, and right middle frontal cortex. The longitudinal study showed that GWR increased around the fusiform, inferior/superior temporal lobe, and entorhinal cortex in MCI and progressed to larger cortical regions after progression to AD. The spatial pattern of GWR-increased regions was independent of β-amyloid deposits but overlapped with tauopathy. The GWR can serve as a promising biomarker of neurodegeneration in AD.

Keywords: GWR; cognitive decline; dementia; imaging biomarker; β-amyloid.

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Conflict of interest statement

None.

Figures

FIGURE 1
FIGURE 1
Between‐group differences in GWR (in the cross‐sectional dataset). Effects of MCI Aβ−, MCI Aβ+, and AD Aβ+ on GWR are shown respectively. Only the significant clusters with corrected p < .05 after permutations are colored. The color bar represents uncorrected p values. Positive p represents a positive difference in the contrast and vice versa. AD Aβ+, dementia with Aβ positivity; CN, cognitively normal participants without Aβ deposition; GWR, gray/white signal intensity ratio; MCI Aβ+, mild cognitive impairment with Aβ positivity.
FIGURE 2
FIGURE 2
Effect of AD Aβ+ on GWR with and without controlling for Aβ deposition. Effects of AD Aβ+ on GWR (a), Aβ deposition measured with PET (b), and GWR after controlling for Aβ SUVR at each vertex along the cortex (c) are shown. The color bar represents uncorrected p values. Positive p values represent a positive difference in the contrast. AD Aβ+, dementia with Aβ positivity; CN, cognitively normal participants without Aβ deposition; GWR, gray/white signal intensity ratio.
FIGURE 3
FIGURE 3
Correlation between GWR and ACER across all clinical participants in MCI Aβ+ and AD Aβ+, AD Aβ+, and MCI Aβ+, respectively. The color bar represents uncorrected p values. Negative p values represent negative correlation and vice versa. ACER, Addenbrooke's Cognitive Examination‐Revised; AD, dementia with Aβ positivity; GWR, gray/white signal intensity ratio; MCI, mild cognitive impairment with Aβ positivity.
FIGURE 4
FIGURE 4
Correlation between GWR and subtests of ACER across all clinical participants in MCI Aβ+ and AD Aβ+. Only the significant clusters with corrected p < .05 after permutations were colored. The color bar represents uncorrected p values. Negative p values represent negative correlation and vice versa. ACER, Addenbrooke's Cognitive Examination‐Revised; AD Aβ+, dementia with Aβ positivity; GWR, gray/white signal intensity ratio; MCI Aβ+, mild cognitive impairment with Aβ positivity.
FIGURE 5
FIGURE 5
Longitudinal changes in GWR in the development of AD. Repeated measures ANCOVA was used to determine if GWR changes over the course of the disease progression (CN to MCI to Dementia). The time interval between visits was set as a covariate. Stretched inflated surface of brain was used as template to show results deep in the sulcus clearly. Only the significant clusters with corrected p < .01 after permutations were colored. The color bar represents uncorrected p values. Positive p values represent a positive difference in the contrast and vice versa. AD, dementia; CN, cognitively normal participants; GWR, gray/white signal intensity ratio; MCI, mild cognitive impairment.
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References

    1. Apostolova, L. G. , Mosconi, L. , Thompson, P. M. , Green, A. E. , Hwang, K. S. , Ramirez, A. , Mistur, R. , Tsui, W. H. , & de Leon, M. J. (2010). Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal. Neurobiology of Aging, 31, 1077–1088. 10.1016/j.neurobiolaging.2008.08.008 - DOI - PMC - PubMed
    1. Carmichael, O. T. , Lopez, O. , Becker, J. T. , & Kuller, L. (2009). Trajectories of brain loss in aging and the development of cognitive impairment. Neurology, 72, 771; author reply 771–772–772. 10.1212/01.wnl.0000339386.26096.93 - DOI - PubMed
    1. Deleglise, B. , Magnifico, S. , Duplus, E. , Vaur, P. , Soubeyre, V. , Belle, M. , Vignes, M. , Viovy, J.‐L. , Jacotot, E. , Peyrin, J.‐M. , & Brugg, B. (2014). β‐Amyloid induces a dying‐back process and remote trans‐synaptic alterations in a microfluidic‐based reconstructed neuronal network. Acta Neuropathologica Communications, 2, 145. 10.1186/s40478-014-0145-3 - DOI - PMC - PubMed
    1. Doré, V. , Villemagne, V. L. , Bourgeat, P. , Fripp, J. , Acosta, O. , Chetélat, G. , Zhou, L. , Martins, R. , Ellis, K. A. , Masters, C. L. , Ames, D. , Salvado, O. , & Rowe, C. C. (2013). Cross‐sectional and longitudinal analysis of the relationship between Aβ deposition, cortical thickness, and memory in cognitively unimpaired individuals and in Alzheimer disease. JAMA Neurology, 70, 903–911. 10.1001/jamaneurol.2013.1062 - DOI - PubMed
    1. Fang, R. , Wang, G. , Huang, Y. , Zhuang, J.‐P. , Tang, H.‐D. , Wang, Y. , Deng, Y.‐L. , Xu, W. , Chen, S.‐D. , & Ren, R.‐J. (2014). Validation of the Chinese version of Addenbrooke's cognitive examination‐revised for screening mild Alzheimer's disease and mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 37, 223–231. 10.1159/000353541 - DOI - PubMed

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